Hitting the bull's-eye
Sorrento Valley's Ambit helps pharmaceutical giants determine drugs' targets
By Terri Somers
UNION-TRIBUNE STAFF WRITER
April 15, 2005
The top executives at Ambit Biosciences clearly remember the heart-stopping angst they felt the day they had to prove the accuracy of their company's technology to the first potential client, a pharmaceutical giant.
"I didn't sleep over the weekend after we sent them the data," chief executive W. Scott Salka recalled recently. "We were so worried that they wouldn't think our baby was as pretty as we thought it was."
Ambit, a privately held company in Sorrento Valley, developed technology that allows it to figure out which targets in a person's body are being affected by a drug molecule.
Drugs generally aim to hit one target, a protein, shutting off a biological process that triggers a disease or triggering a beneficial process. However, drugs sometimes hit unintended proteins as well, shutting off normal biological processes and sometimes causing unpleasant side effects.
Drug companies are willing to pay for such a service as Ambit's because federal regulators want to know as much as they can about all the affected targets before deciding whether to approve a drug for market, Ambit president David Lockhart said.
Ambit's first potential client, GlaxoSmithKline, had asked the company to determine the targets of several molecules. The pharmaceutical giant knew the answers already, Lockhart recalled.
He remembers the telephone call with GlaxoSmithKline, going over Ambit's results. As the pharmaceutical representative read off a checklist of the targets, Lockhart said, his hands shook. His breath hinged on every response.
Ambit's test results were accurate.
Additional proof of its reliability, Lockhart said, is seen in the drug compounds the company hopes to begin testing in humans next year, as well as the company's ongoing collaborations with drug giants GlaxoSmithKline, Roche Pharmaceuticals and Bristol-Myers Squibb.
Roche also was an investor in an Ambit financing round that raised a total of $32 million. Among the company's other investors are Avalon Ventures and Forward Ventures, venture capital funds active in the San Diego region's biotechnology sector.
The company's technology, which concentrates on a specific type of protein in the body called a kinase, recently was explained in an article inthe journal Nature Biotechnology. There are more then 500 kinase proteins listed on the human genome, the genetic map of the human body.
The proteins are considered important targets in drug discovery because they are known to be linked to a number of serious diseases, including cancer and inflammation.
Ambit is not the only company with expertise in such technology. Invitrogen, a successful biotechnology tool company based in Carlsbad, and Atlanta-based Serologicals can also test hundreds of kinases. However, Ambit claims to be able to run more tests in a shorter time and for less money.
Kevin Kinsella of Avalon Ventures recalled when he first got excited about the technology that would persuade him to become founder of Ambit.
He received a telephone call from David Austin, a professor at Yale.
Austin said he had developed a technology that allowed him to go fishing for successful drugs by throwing a potential drug candidate into a soup "of proteins and seeing what it attracted," Kinsella said.
Such a technology would be significant because there are hundreds of drugs that are on the market that are effective, but for which no one really knows which protein they interact with. In other words, their targets are a mystery.
Additionally, in the wake of drug side-effect problems such as the ones recently reported with best-selling painkillers Bextra and Celebrex, the Food and Drug Administration wants to be able to trace backward from the side effects to figure out what went wrong, Kinsella said.
Austin mentioned one key experiment that really excited Kinsella: The scientist said that within a week, with the help of a few other scientists in his lab, the technology allowed them to find the target of FK506, an immunosuppressant drug used by people with liver transplants. The experiment had cost just a few hundred dollars, Kinsella said.
About eleven years earlier, Kinsella's company Vertex had spent millions of dollars and more than a year trying to find the drug's target.
It was the proof he needed to found the company and begin looking for other investors.
Lockhart, a former post-doctorate fellow at the Whitehead Institute for Biomedical Research and the Biology Department at Massachusetts Institute of Technology, was hired as president and chief science officer. After his postdoctoral training, Lockhart worked at the biotechnology company Affymetrix for five years as vice president of genomics research.
He later served a year as director of genomics at the Genomics Institute of the Novartis Research Foundation in San Diego.
In January 2001, Salka, a co-founder of one of the first commercial genomics companies, Sequana Therapeutics, was hired as chief executive officer. Besides running two other private biotech genomic companies, Salka served in the Army's Special Forces as an adviser to several Central American governments on matters of internal defense.
Around the time both men were hired, the frenzy over biotechnology "tool" companies was waning. Investors were realizing that these tools were not getting drugs to market faster. It became apparent it would be hard to keep such companies afloat.
Ambit never had the intention of becoming a tool company, Salka said during a recent interview. Developing a drug pipeline is where there is potential for money, excitement and a future, he said.
But selling the use of the company's technology to other drug-development companies would create a revenue stream that would help the company fund research that would lead to its own drug pipeline, he said.
"Think of us as a customer of our own technology," Salka said.
By January 2002, the company had its first nibbles from big pharmaceutical companies: It was asked to do pilot studies to find the targets hit by a few molecules. But the pharmaceutical companies did not want to pay for these test studies, Salk said.
Ambit refused to do any work for free. Eventually the handful of pilot studies they were hired to complete brought in a revenue stream in the range of hundreds of thousands of dollars, he said.
The deal with Roche, signed in August, was the company's first significant multiyear, multimillion-dollar collaboration, Salka said. He declined to specify the dollar amount.
The company has used its technology to develop drug candidates that it hopes to move into human trials by the beginning of next year, Salka said. The first compound, for the treatment of stroke, was developed through a combination of deductive reasoning and research.
Lockhart said Ambit scientists noted that patients taking Lipitor, a cholesterol-lowering statin drug made by Pfizer, had a 20 percent decrease in the incidence of stroke. That indicated that the drug, unlike any other statin, was hitting an unknown secondary target that had something to do with stroke, he said.
The company set about finding which target the drug was hitting that other drugs were not. After finding the target, the company developed a compound that hits just that target. Unlike Lipitor, this molecule is not a statin, Lockhart said.
"Now we have a precisely targeted small molecule, which means it is more effective in smaller amounts," he said. Pre-clinical studies show that besides being a preventive medicine, it can be used to treat patients up to six hours past the onset of their stroke, he said.
By the second quarter of 2006, the company hopes to start human trials of a drug for acute myeloid leukemia, a blood cancer common in adults and children.
With the closing of its latest round of financing, bringing Ambit's investment to $50 million total, the company has enough money to get to the end of Phase 2 trials on both drugs, he said. But it will have to partner with a larger company to fund final-stage Phase 3 trials, which will cost between $150 million and $200 million, Salka said.
[Edit: ambitbio.com ]
Terri Somers: (619) 293-2028; terri.somers@uniontrib.com |
